ASCO 2023: Identifying Potentially Targetable Gene Mutations in Intrahepatic Cholangiocarcinoma

By: Kayci Reyer
Posted: Friday, June 23, 2023

Findings from the multicenter BILCAP trial, which were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4019), suggest that a variety of cancer driver genes and targetable mutations may be found among patients with intrahepatic cholangiocarcinoma. Results from the phase III trial found that patients with certain mutations, including fusions or amplifications, may experience poorer outcomes.

“MET amplification, NTRK1 amplification, and FGFR3 fusions may be important indicators in determining prognosis and could provide attractive targets for future targeted anticancer therapy in [intrahepatic cholangiocarcinoma],” concluded John A. Bridgewater, MD, PhD, of University College London, and colleagues.

The study collected and performed DNA and RNA extraction on archived fixed-formalin tissue samples from enrolled patients, 84 of whom had intrahepatic cholangiocarcinoma. Among that subset, samples from 45 patients underwent additional low-pass whole-genome sequencing plus RNA sequencing, and 36 of the 345 also underwent targeted gene sequencing. Many samples were found to harbor fusions, including FGFR2 (20%), NTRK1 (6.7%), FGFR1 (6.7%), FGFR3 (4.4%), and FGFR4 (4.4%). Mutations were identified in driver genes ROS1 (33.3%), MET (27.8%), and ALK (19.4%), and known pathogenic variants were observed in IDH1, BRAF, FGFR2, FGFR3, IDH2, and EGFR. Amplifications were commonly found in NTRK1, ERBB2, and MET genes.

Though most observed alterations did not seem to meaningfully impact survival or clinical outcomes, FGFR3 fusion significantly reduced overall survival (overall survival hazard ratio [HR] = 6.57, P = .0091), according to the investigators. Overall survival was substantially lower, and risk of recurrence substantially higher, for patients harboring four or more copies of NTRK1 (overall survival HR = 3.55, P = .0027; recurrence HR = 3.71, P = .0734) or MET (overall survival HR = 6.06, P < .001; recurrence HR = 6.05, P < .001). Roughly half of the study patients (51.1%) received capecitabine treatment.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2023 ASCO Annual Meeting

---